The present invention relates to a device and method for controlling or eliminating tissue remodeling or proliferation, and in particular to a balloon catheter for controlling or eliminating tissue remodeling or proliferation.
Cryotherapy, the therapeutic use of cold, is known in the medical field. Some of the well defined applications of cryotherapy include the following:
(1) Tissues collected from bovine, pigs, or sheep are preserved at reduced temperature so that the elastic membrane or elastin present in the tissues is protected for subsequent applications. Without the use of such temperature reduction, the tissues dry out and lose their original mechanical, physical and chemical properties.
(2) During open heart surgery, when the heart is opened to either replace a valve or an underlying diseased coronary artery, the myocardium or the tissues surrounding the heart are exposed to reduced temperature by dipping them in ice or sub-cooled water while the surgery is underway to preserve them.
(3) During open heart surgery, when the aorta is cross-clamped and blood from the heart is directed into a heart-lung machine, the blood is mixed with cold cardioplegia solution to preserve the cells and other essential components in the blood, an especially critical procedure when the surgery is lengthy.
(4) Bovine and other homograft valves that have been preserved in cryo-based solutions and reduced temperature environment have been shown to have superior performance during long term follow-up studies when compared with mechanical bileaflet or single leaflet valves.
(5) In many pain management therapeutic situations, the area or region of acute pain is exposed to reduced temperature fluids or xe2x80x9ccold packsxe2x80x9d to reduce nerve damage and relieve pain.
(6) External probes have been used in the treatment of endometrial ablation and for prostate treatment. These probes are connected to a cryogenerator and the probe tips are used to treat the tissues in the open areas of the body.
(7) Treating arrhythmia with exterior probes has been described in various situations. When the chest is opened during bypass surgery, sudden arrythmias situations have been treated by putting cold probes on the myocardial tissue to restore cardiac flow. These applications are currently done using intra-cardiac catheters to spot the areas of myocardial viability and to target the cryo-probes to the unviable zones. These are usually non-balloon cryo-applications.
The present invention is directed to the use of cryotherapy for reducing tissue injury after balloon angioplasty or stent implantation. One of the most common causes of failure of angioplasty or stent implantation is restenosis. Restenosis is evidenced when the artery re-occludes due to tissue ingrowth and/or elastic recoil of the arterial wall at the site of the prior occlusion. After a balloon angioplasty procedure or stent implantation procedure has been completed, the arterial wall often exhibits damage or inflammation due to the required use of force from inflation of a balloon catheter against the cellular layers of the arterial wall. Specifically, when a balloon is inflated at the site of a lesion where the artery is occluded, the lesion is mechanically pushed up by force acting thereon due to inflation of the balloon. Pathology of experiments in pigs and sheep reveals that the balloon inflation causes endothelial injury as well as tissue dislodgement at the site of the lesion. Such an injury is characterized by inner lumen wall cracks that are filled up with blood and some thrombus (clotting material). These cracks may infiltrate into the second and third layers of the vessel wall that are termed adventitia and media primarily composed of collagen, smooth muscle cells and elastic cells that contribute to the compliance of the artery.
When these layers are disrupted due to balloon inflation or stent implantation, compliance response is lost. This results in proliferation of cells as a function of time. Although the proliferation starts immediately after the injury to the arterial wall, maximum proliferation may be observed 6 to 18 months after the initial injury.
The present invention is also directed to a device and method for using cryotherapy in any clinical situation in which the modeling or proliferation of tissue needs to be controlled or eliminated. These clinical situations may be vascular or non-vascular applications, and may include coronary or non-coronary applications. For example, the device and method according to the present invention can be used to treat cancer by terminating angiogenesis, i.e the formation of a network of capillaries and veins around or inside a cancerous tumor.
In addition to the use of temperature, other forms of energy such as light or radiation can be used to control or eliminate tissue remodeling or proliferation. In photodynamic therapy, light is combined with a photosensitive drug. In this regard, the present invention is also directed to a balloon catheter for photodynamic therapy or radiation delivery.
The present invention relates to a catheter for controlling tissue remodeling or proliferation at a tissue site. The catheter includes an outer balloon located on a distal end of the catheter, a first lumen in fluid communication with the outer balloon and fluidly connected to a source of liquid for expanding the outer balloon with liquid to contact the tissue site, and a second lumen fluidly connected to a source of coolant fluid at a proximal end for transporting the coolant fluid to a distal end of the second lumen to cool the liquid in the outer balloon and thereby the tissue site to a cryo-therapeutic temperature. In a preferred embodiment, the coolant fluid temperature is sufficient to freeze the liquid after expansion through the orifice. The second lumen includes an orifice configured and dimensioned to allow the coolant fluid to expand as it passes therethrough to reduce coolant fluid temperature.
Preferably, the outer balloon has a temperature sensor for monitoring the temperature of the tissue site and there is a valve between the fluid coolant source and the second lumen for controlling introduction of the coolant gas into the second lumen.
The catheter may include an inner balloon in fluid communication with the distal end of the second lumen in close proximity to the outer balloon. The fluid communication between the second lumen and the inner balloon is through the orifice to allow the coolant fluid to expand into the inner balloon. The catheter may also include a third lumen configured and dimensioned to receive a guide wire for directing the catheter to the tissue site.
In order to facilitate removal of coolant fluid from the inner balloon, the catheter may have a fourth lumen in fluid communication with the inner balloon at a distal end. This fourth lumen may be fluidly connected to a vacuum to assist in removing the coolant fluid from the inner balloon.
In another embodiment, the catheter has a first lumen configured and dimensioned to receive a guide wire for directing the catheter to the tissue site, an outer balloon located on a distal end of the catheter, a second lumen in fluid communication with the outer balloon at a distal end and fluidly connected to a source of a media at a proximal end for expanding the outer balloon with the media so that the outer balloon is in contact with the tissue site. The media is normally in an inactive state in which the media has no effect on tissue remodeling or proliferation, but can be transformed to an active state upon addition of energy in which the media effects tissue remodeling or proliferation. The catheter also includes an inner balloon located on the distal end of the catheter and in close proximity to the outer balloon and a third lumen in fluid communication with the inner balloon at a distal end and fluidly connected to a source of an activation factor at a proximal end for transporting the activation factor to the inner balloon to provide the energy needed to transform the media to the active state.
The activation factor may be light, heat, or some other form of energy. Preferably, the media includes a well-tolerated fluid such as saline. The media may also include a substance that is radioactive in the active state.
In another embodiment, an outer balloon located on a distal end of the catheter has a coating of a media. The media is normally in an inactive state in which the media has no effect on tissue remodeling or proliferation and is transformable upon addition of energy to an active state in which the media affects tissue remodeling or proliferation. The catheter also includes a second lumen in fluid communication with the outer balloon at a distal end and fluidly connected to a source of fluid at a proximal end for expanding the outer balloon with the media so that the outer balloon is in contact with the tissue site, an inner balloon located on the distal end of the catheter and in close proximity to the outer balloon, and a third lumen in fluid communication with the inner balloon at a distal end. The third lumen is configured and dimensioned to receive a source of an activation factor at a proximal end for providing the energy needed to transform the media to the active state. The coating can be either on an outer surface of the outside balloon in contact with the tissue or an inner surface of the outside balloon. The coating may include bromide or iodide.
The present invention also relates to a method for controlling tissue remodeling or proliferation at a tissue site. The method includes the steps of fluidly connecting a quantity of cryo-medium to a catheter having at least two lumens; inserting the catheter into a patient and conveying it to the tissue site; dispensing the cryo-medium through a lumen having a plurality of holes at a distal end to deliver the cryo-medium to the tissue site; providing an inflatable balloon for securing the catheter to the site, the balloon having an outer impervious wall and an inner wall with holes therein; and conveying the cryo-medium between the outer and inner walls and in through the holes.
Preferably, the cryo-medium is maintained at a temperature below 14xc2x0 C. In one embodiment, the cryo-medium is passed through an orifice to reduce the temperature of the cryo-medium. The catheter may have two spaced balloons, inflatable upstream and downstream of the tissue site. The catheter may also be provided with an inner passageway with a closed distal end and a peripheral wall with holes therein so that the cryo-medium may be dispensed through the holes.